Essential fatty acid (EFA) and their derivatives are divided into two group; alpha linolenic acid which is the precursor of n-3 polyunsaturated fatty acids (PUFA) and linoleic acid which is the precursor of the n-6 PUFA. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the n-3 PUFA metabolites that have been shown to have potent anti-inflammatory properties acting through transcription factors and gene expression, calcium fluxes, alter membrane fluidity, the regulation and secretion of digestive enzymes and hormones and they also play a role in decreasing susceptibility to inflammatory diseases, such as arthritis and asthma (Das U. N. 2006. Biotechnol J., 1(4):420-439). In contrast arachidonic acid (AA), an n-6 PUFA metabolite, stimulates pro-inflammatory reactions through various prostaglandins and leukotriennes pathways. Gilljam and colleagues studied the role of AA on lung inflammation and infection and discovered a considerable increase in mucus (Gilljam et al., 1986. Scand J Clin Lab Invest. 46(6): 511-8). This increase in inflammation was not secondary to the lung infection but a primary defect attributable to the Cftr gene mutation(s). Epidemiological, clinical, and biochemical studies suggest that the beneficial effects of consuming n-3 PUFA is generally considered to be due to the reduction of AA and its eicosanoid metabolites. DHA and AA are the “yin and yang” of fatty acid metabolism, and disruption of the n-3: n-6 EFA balance results in a number of systemic abnormalities (Das U. N., supra).
Cystic Fibrosis (CF) is characterized by excessive lung inflammation followed by recurrent bacterial infections. At the root of this condition is a defective gene that prevents cells from producing functional Cystic Fibrosis Transmembrane Conductance Regulator proteins (CFTR). The CFTR gene encodes a 1,480 amino acids protein. The most common mutation found in CF patient is deltaF508 (ΔF508); it is a deletion of 3 nucleotides that results in a loss of the amino acid phenylalanine (F) at position 508 of the protein. There are several other mutations which have been associated with CF (Nunes et al., 1991. Hum. Genet. 87(6): 737-8; Estivill X. et al., 1997. Hum. Mutat., 10(2) 135-54). The missing or non-functional CFTR undermine the body's immune system, cause hyperinflammation and cause the body to produce abnormally thick, sticky mucus that clogs the small airways of the lungs and leads to life-threatening lung infections. These thick secretions obstruct other exocrine glands, including the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food. Also, CF patients suffer from a lipid imbalance in the CF-affected organs (Sahu & Lynn (1977) Am. Rev. Respir. Dis. 115:233-239)
Another recently described phenotype associated with CF is reduced bone mineral density, which results in osteopenia and osteoporosis (Gronowitz, E. et al., 2006. Br. J. Nutr. 95:1159-1165; Cawood, T. J. et al., 2005. Ir. Med. J. 98:270-273; Giron, R. M. et al., Med. Clin. (Barc.) 125:325-328; Conway, S. 2003. J. Cyst. Fibros. 2:161-162; Giron, R. M. et al., 2004. Med. Clin. (Barc.) 123:81-84; Flohr, F. et al., 2002. Eur. J. Endocrinol. 146:531-536; Robinson, R. F. et al., 2001. J. Pediatr. Health Care 15:308-315). Osteopenia refers to decreased calcification or density of bones. Osteoporosis literally means “porous bones” and is characterized by low bone density and the structural weakening of bone tissue, which leads to an increased risk of fractures (Turner, C. H. 2006. Ann. N.Y. Acad. Sci. 1068:429-46). Currently, osteoporosis treatment regimen for patients with CF consists of a cocktail of medications including: vitamin D, calcium, vitamin K, sex hormones, anti-resorptive agents such as bisphosphates, anabolic agents such as parathyroid hormone (PTH) and human recombinant growth hormones (HrGH) (Hecker, T. M. and Aris, R. M. 2004. Drugs. 64:133-147; Robinson, R. F., and Nahata, M. C. 2001. J. Pediatr. Health Care. 15:308-315).
There is a need for the development of novel strategies for the diagnosis and treatment of diseases and conditions associated with lipid imbalance.
The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety.